GSP-2, a polysaccharide extracted from Ganoderma sinense, is a novel toll-like receptor 4 agonist.
Ganoderma sinense is a Chinese unique medicinal fungus that has been used in folk medicine for thousands of years. Polysaccharides are considered to be biologically active ingredients due to their immune-modulating functions. Previously we found that GSP-2, a new polysaccharide isolated from Ganoder...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0221636 |
| _version_ | 1819111788137938944 |
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| author | Kai-Sheng Liu Cheng Zhang Hong-Liang Dong Kai-Kai Li Quan-Bin Han Yong Wan Rui Chen Fang Yang Hai-Li Li Chun-Hay Ko Xiao-Qiang Han |
| author_facet | Kai-Sheng Liu Cheng Zhang Hong-Liang Dong Kai-Kai Li Quan-Bin Han Yong Wan Rui Chen Fang Yang Hai-Li Li Chun-Hay Ko Xiao-Qiang Han |
| author_sort | Kai-Sheng Liu |
| collection | DOAJ |
| description | Ganoderma sinense is a Chinese unique medicinal fungus that has been used in folk medicine for thousands of years. Polysaccharides are considered to be biologically active ingredients due to their immune-modulating functions. Previously we found that GSP-2, a new polysaccharide isolated from Ganoderma sinense, exerts an immunomodulatory effect in human peripheral blood mononuclear cells but the underlying mechanism is unclear. The present study aimed to investigate how GSP-2 triggers immunologic responses and the implicated signaling pathways. GSP-2 effects were investigated both in a macrophagic cell line, RAW264.7, and in primary macrophages. Moreover, the molecular basis of GSP-2 recognition by immune cells, and the consequent activation of signaling cascades, were explored by employing recombinant human HEK293-TLR-Blue clones, individually overexpressing various Toll-like receptors. GSP-2 dose-dependently induced the overexpression of Toll-like receptor 4 (TLR4) but did not affect the expression of other TLRs. Moreover, GSP-2 induced TNFα secretion in primary macrophages from wild-type, but not TLR4-knockout mice. In addition, GSP-2 upregulated TLR4 protein expression and activated the MAPK pathway in RAW246.7 macrophages. Finally, GSP-2 induced the production of the cytokines TNFα, IL1β, and IL6. Our data demonstrated that GSP-2 was specifically recognized by TLR4, promoting cytokine secretion and immune modulation in macrophages. |
| first_indexed | 2024-12-22T04:03:10Z |
| format | Article |
| id | doaj.art-30abaa24c7dc4249b218cb7a9cc350b3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T04:03:10Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-30abaa24c7dc4249b218cb7a9cc350b32022-12-21T18:39:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01148e022163610.1371/journal.pone.0221636GSP-2, a polysaccharide extracted from Ganoderma sinense, is a novel toll-like receptor 4 agonist.Kai-Sheng LiuCheng ZhangHong-Liang DongKai-Kai LiQuan-Bin HanYong WanRui ChenFang YangHai-Li LiChun-Hay KoXiao-Qiang HanGanoderma sinense is a Chinese unique medicinal fungus that has been used in folk medicine for thousands of years. Polysaccharides are considered to be biologically active ingredients due to their immune-modulating functions. Previously we found that GSP-2, a new polysaccharide isolated from Ganoderma sinense, exerts an immunomodulatory effect in human peripheral blood mononuclear cells but the underlying mechanism is unclear. The present study aimed to investigate how GSP-2 triggers immunologic responses and the implicated signaling pathways. GSP-2 effects were investigated both in a macrophagic cell line, RAW264.7, and in primary macrophages. Moreover, the molecular basis of GSP-2 recognition by immune cells, and the consequent activation of signaling cascades, were explored by employing recombinant human HEK293-TLR-Blue clones, individually overexpressing various Toll-like receptors. GSP-2 dose-dependently induced the overexpression of Toll-like receptor 4 (TLR4) but did not affect the expression of other TLRs. Moreover, GSP-2 induced TNFα secretion in primary macrophages from wild-type, but not TLR4-knockout mice. In addition, GSP-2 upregulated TLR4 protein expression and activated the MAPK pathway in RAW246.7 macrophages. Finally, GSP-2 induced the production of the cytokines TNFα, IL1β, and IL6. Our data demonstrated that GSP-2 was specifically recognized by TLR4, promoting cytokine secretion and immune modulation in macrophages.https://doi.org/10.1371/journal.pone.0221636 |
| spellingShingle | Kai-Sheng Liu Cheng Zhang Hong-Liang Dong Kai-Kai Li Quan-Bin Han Yong Wan Rui Chen Fang Yang Hai-Li Li Chun-Hay Ko Xiao-Qiang Han GSP-2, a polysaccharide extracted from Ganoderma sinense, is a novel toll-like receptor 4 agonist. PLoS ONE |
| title | GSP-2, a polysaccharide extracted from Ganoderma sinense, is a novel toll-like receptor 4 agonist. |
| title_full | GSP-2, a polysaccharide extracted from Ganoderma sinense, is a novel toll-like receptor 4 agonist. |
| title_fullStr | GSP-2, a polysaccharide extracted from Ganoderma sinense, is a novel toll-like receptor 4 agonist. |
| title_full_unstemmed | GSP-2, a polysaccharide extracted from Ganoderma sinense, is a novel toll-like receptor 4 agonist. |
| title_short | GSP-2, a polysaccharide extracted from Ganoderma sinense, is a novel toll-like receptor 4 agonist. |
| title_sort | gsp 2 a polysaccharide extracted from ganoderma sinense is a novel toll like receptor 4 agonist |
| url | https://doi.org/10.1371/journal.pone.0221636 |
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